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Id2 deficiency promotes metastasis in a mouse model of ocular cancer

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Abstract

The inhibitor of DNA binding 2 (Id2) basic helix-loop-helix protein interacts genetically and physically with the pocket proteins (Rb, p107 and p130) and has been implicated as an oncogene. In other studies, however, Id2 has been shown to function as a tumor suppressor. Here, we studied the role of Id2 in a well characterized model of ocular cancer in which the three pocket proteins are inactivated by generating mice lacking one or both Id2 alleles. Id2 deficiency had no impact on tumorigenesis in the eye. Unexpectedly, however, Id2 loss significantly increased the rate of metastasis. Liver metastases in Id2 heterozygotes demonstrated significant decrease of Id2 expression and loss of the remaining Id2 allele, strongly suggesting that Id2 inactivation specifically was required for metastasis in this model. These findings provide new insights into the role of Id2 in metastasis.

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Abbreviations

Id2:

Inhibitor of DNA binding 2

Rb:

Retinoblastoma

bHLH:

Basic helix-loop-helix

SV40:

Simian virus 40

TAg:

Large and small tumor antigens

RPE:

Retinal pigment epithelium

gDNA:

Genomic DNA

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This research was supported by R01 EY1316905 from the National Eye Institute, Knights Templar Foundation, Research to Prevent Blindness, Horncrest Foundation (JWH), and departmental grants from Research to Prevent Blindness and National Eye Institute Vision Core Grant P30 EY 02687. The authors thank the Immunomorphology Core Lab for preparation of histopathologic sections.

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Authors and Affiliations

  1. Department of Ophthalmology & Visual Sciences and Siteman Cancer Center, Washington University School of Medicine, Campus Box 8096, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Olga A. Agapova, Erica Person & J. William Harbour

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  1. Olga A. Agapova
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  2. Erica Person
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  3. J. William Harbour
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Correspondence to J. William Harbour.

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Agapova, O.A., Person, E. & Harbour, J.W. Id2 deficiency promotes metastasis in a mouse model of ocular cancer. Clin Exp Metastasis 27, 91–96 (2010). https://doi.org/10.1007/s10585-010-9304-5

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  • DOI: https://doi.org/10.1007/s10585-010-9304-5

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